We have recently identified and partially characterized a peptidase from human postmortem cerebral cortex that is highly active toward luteinizing hormone-releasing hormone (LH-RH) and probably other neuropeptides including angiotensin II, bradykinin, and neurotensin, but not somatostatin. We propose in this application to: 1) Purify to homogeneity this neuropeptide-degrading enzyme from postmortem human cerebral cortex. 2) Characterize this enzyme in terms of molecular weight, subunit structure, pH optimum, Michaelis-Menton kinetics, behavior in the presence of enzyme inhibitors or activators, and bond and substrate specificities. 3) Raise and characterize an antiserum against the purified enzyme as an initial step toward further investigating the biological role of the enzyme. Based upon preliminary data, the purification procedures will include anion-exchange and gel-filtration chromatography as well as affinity chromatography on organomercurial-Sepharose. Other aspects of the study will employ SDS-polyacrylamide gel electrophoresis, radioimmunoassay for LH-RH, and high performance liquid chromatography. Our long-term objectives are to elucidate the biological role of this enzyme and similar peptidases in normal brain function and to determine the involvement of these enzymes in neuropsychiatric disorders.